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Hearing Gene Therapy Moves Beyond a Rare-Disease Niche: First Child Dosed With GJB2 Therapy
Skylark Bio is expanding inner-ear gene therapy from rare OTOF deficiency to the more common GJB2-related hearing loss; the first participant has been dosed, but efficacy, durability, and surgical risks remain to be answered by a small early-stage trial.
Gene therapy for congenital hearing loss is moving from extremely rare causes toward a much broader patient population. Skylark Bio announced that the first child has received SKY-GJB2 treatment in the SONIX trial. This marks the company’s first clinical advance since emerging from stealth and formally brings GJB2, a common cause of hereditary nonsyndromic hearing loss, into human trials.
GJB2 produces connexin 26, which helps inner-ear cells maintain normal signal transmission and environmental balance. Children with two pathogenic or likely pathogenic GJB2 variants may have bilateral sensorineural hearing loss from birth. SKY-GJB2 uses an optimized adeno-associated virus vector to deliver a functional gene to affected cells in the cochlea, with the aim of restoring some hearing function by addressing the underlying cause.
According to the clinical trial registry, SONIX is a Phase 1/2, open-label, nonrandomized study expected to enroll 10 children aged 9 months to 7 years. The therapy is administered to only one ear, using the single-use SKY-CAT device to inject the drug into the cochlea. The study will first enroll four children aged 2 to 7 years, followed by an evaluation of six children younger than 2 years.
The trial’s primary objective is not to demonstrate efficacy, but to document adverse events related to the gene therapy, the intracochlear administration procedure, and the delivery device. Researchers will also track changes in auditory brainstem response thresholds and assess after surgery whether SKY-CAT can complete delivery safely and effectively. The registry estimates that the primary study phase will be completed by the end of 2027, with the overall trial continuing through 2028.
The significance of this program lies in the fact that the most closely watched gene therapies for congenital deafness currently largely target OTOF, the gene encoding otoferlin. In early studies, these therapies have shown that some children can achieve hearing improvement, but OTOF accounts for only a small proportion of hereditary deafness. GJB2 variants, by contrast, are among the most common causes of hereditary nonsyndromic hearing loss worldwide, so if the technology proves successful, the potential eligible population could expand substantially.
However, the two cannot be directly compared. GJB2 involves cochlear supporting cells and complex intercellular connections, presenting biological challenges different from restoring OTOF protein in specific sensory cells. The therapy must also demonstrate that the vector can reach the correct cells, that gene expression is sufficient and durable, and that residual hearing is not damaged. The unilateral treatment design helps control early risks, but it also limits how initial results can be interpreted in terms of everyday binaural hearing function.
Publicly available information currently confirms only that the first participant has been dosed; no safety or hearing-improvement data are yet available. An open-label study of 10 participants can provide preliminary signals, but cannot determine the long-term effects, whether different GJB2 variants respond consistently, or how the therapy should be combined with hearing aids or cochlear implants. Its true clinical value will still need to be established through subsequent follow-up and larger studies.